a Department of Pharmacology, Toxicology, and Therapeutics , University/BHF Centre for Cardiovascular Science, University of Edinburgh , Edinburgh , UK.
b National Poisons Information Service - Edinburgh , Royal Infirmary of Edinburgh , Edinburgh , UK.
Clin Toxicol (Phila). 2018 Nov;56(11):1098-1106. doi: 10.1080/15563650.2018.1455978. Epub 2018 Mar 28.
Iron poisoning is potentially serious, but mortality has fallen worldwide since implementation of pack size and packaging restrictions, and changes in iron use during pregnancy. The management of individual cases of overdose remains problematic due to uncertainty about indications for antidote. We examine the epidemiology of iron overdose in hospital cases referred to the UK National Poisons Information Service (NPIS) and evaluate the toxicokinetics of iron in patients ingesting only iron preparations. Anonymized hospital referral patient data from the NPIS database were collated for the period 1 January 2008 to 31 July 2017. Information was extracted, where recorded, on type of ingestion [iron alone (single), or combined with other agents (mixed)], reported dose, iron salt, timed iron concentrations and symptoms. In single-agent ingestions, the relationships between reported elemental iron dose, early concentrations (4-6 h), and symptoms were evaluated in teenagers and adults (≥13 years) and children (≤12 years) using standard statistical techniques (correlation and unpaired nonparametric comparisons). In those patients with sufficient sample points (three or more), a simple kinetic analysis was conducted. Of 2708 patients with iron overdoses referred by UK hospitals for advice during the 9.7 years study period, 1839 were single-agent ingestions. There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%) were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years (91% females), the latter a substantial excess over the proportion in the totality of hospital referrals to the NPIS in the same period (13-20 years: 23,776/144,268 16.5%; 67.5% female) ( < .0001 overall and for female %). In 475 teenagers and adults and 86 children, with at least one-timed iron concentration available, there was no correlation between stated dose and iron concentration measured 4-6 h post-ingestion. Observed peak iron concentrations were not related to reported symptoms in adults. Initial iron concentrations were significantly higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO) compared to those that did not [no DFO: mean 63.8 μmol/L (95% CI 62.1-65.6), median 64; DFO: mean 78.5 μmol/L (95% CI 69.2-87.7), median 78.1; Mann-Whitney < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. Single-agent iron exposures reported from UK hospitals were most common in children <5 years and young people aged 13-20 years. Poisoning with organ failure was not identified and there were no fatalities. No correlations were observed between reported iron doses and early concentrations, or between iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.
铁中毒可能很严重,但自实施包装大小和包装限制以及怀孕期间铁使用的变化以来,全球死亡率已经下降。由于不确定解毒剂的适应症,个别过量用药的处理仍然存在问题。我们研究了英国国家毒物信息服务处(NPIS)转介的医院病例中铁过量的流行病学,并评估了仅摄入铁制剂的患者中铁的毒代动力学。 从 2008 年 1 月 1 日至 2017 年 7 月 31 日,从 NPIS 数据库中整理了匿名的医院转介患者数据。提取了记录的摄入类型[单独铁(单一)或与其他药物混合(混合)]、报告剂量、铁盐、定时铁浓度和症状的信息。在单一药物摄入的情况下,使用标准统计技术(相关性和非配对非参数比较)评估青少年和成年人(≥13 岁)和儿童(≤12 岁)中报告的元素铁剂量、早期浓度(4-6 小时)和症状之间的关系。对于具有足够样本点(三个或更多)的患者,进行了简单的动力学分析。 在研究期间的 9.7 年中,英国医院因咨询而转介的 2708 名铁过量患者中,有 1839 名是单一药物摄入。单一药物暴露的年龄发病率有两个高峰;539/1839(28.4%)<6 岁(54.1%为男性),675/1839(36.7%)为 13 至 20 岁(91%为女性),后者与同期 NPIS 向医院转介的总人数相比明显过多(13-20 岁:23776/144268,16.5%;女性占 67.5%)(总体和女性为<.0001)。在 475 名青少年和成年人以及 86 名儿童中,至少有一个定时铁浓度可用,摄入后 4-6 小时测量的铁浓度与报告的剂量之间没有相关性。成年人的观察到的峰值铁浓度与报告的症状无关。接受去铁胺(DFO)治疗的 30 名患者(25 名成年人,5 名儿童)的初始铁浓度明显高于未接受 DFO 治疗的患者[无 DFO:平均 63.8 μmol/L(95%CI 62.1-65.6),中位数 64;DFO:平均 78.5 μmol/L(95%CI 69.2-87.7),中位数 78.1;Mann-Whitney <.0018)。在治疗前,DFO 治疗组和未治疗组之间未观察到症状存在显著差异。该队列中没有患者死亡。 英国医院报告的单一药物铁暴露在<5 岁的儿童和 13-20 岁的年轻人中最为常见。未发现与器官衰竭有关的中毒,也无死亡病例。在该轻度至中度中毒的队列中,未观察到报告的铁剂量与早期浓度之间或铁浓度与症状之间的相关性。